An interventional study of Active Intervention and Placebo Intervention in Hemispatial Neglect, sponsored by KU Leuven. Terminated at 2 sites in Belgium. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-02-21.
Sponsored by KU Leuven · Not applicable, Interventional, and Treatment
Hemispatial neglect is a post-stroke condition in which patients fail to detect stimuli presented on the side of space opposite to the damaged brain hemisphere (contralesional space). To date, there is no established effective treatment for this condition. A virtual reality (VR) behavioral training for the attention deficits characteristic of patients with hemispatial neglect was developed. Patients are stimulated in the visual and auditory modality to orient towards the contralesional side and are rewarded for detecting targets on this side in this training. In the current study the researchers aim to answer two main questions: 1) how feasible is a VR game-based intervention in stroke patients? and 2) what is the efficacy of the virtual reality game-based intervention in reducing the attention deficits characteristic of hemispatial neglect? To answer these questions a randomized partially double-blind placebo-controlled crossover study will be conducted. Two within-subject conditions will be compared: in the active condition patients will play a VR game in which multisensory stimulation is progressively presented in the neglected region (the location where previously presented targets were missed by the patient) and in the placebo condition patients will play a VR game in which the stimulation is presented in the center of of the VR environment. Neglect symptoms will be measured on a two-daily basis to establish the trend of symptom recovery through time. The hypothesis states that symptoms will recover more quickly when patients receive the active version of the VR intervention compared to the placebo version of the VR intervention.
SAMPLE SIZE ESTIMATION:
Power analysis was performed with the SIMR package in R which estimates power for generalized linear mixed models using Monte Carlo simulations. The main analysis will compare the evolution through time of the primary outcome variable between the two within-subject conditions placebo and active intervention. Power was estimated as a function of the number of patients who complete the entire study protocol and as a function of the number of assessment moments per patient. In addition, the power analysis was run under the assumption that the measurement error (residual variance) would be equal to 0.20 SDs. The latter implies that the outcome variable must have a reliability of at least .80. The power analysis revealed that 8 patients need to complete the entire study protocol (per-protocol sample size) - when the study protocol involves a 1-day in-between assessment schedule - to detect a moderate effect size (SD = 0.5) with a type I error rate of 1% and a power of 80%. Thus, for each counterbalancing group a minimum of 4 patients is needed. Assuming that 50% of all patients allocated to a counterbalancing group drop-out at some time point during the study, a total of 16 patients will be recruited to obtain a large enough per-protocol sample size.
MISSING DATA HANDLING:
Missing data can occur when patients do not take part in one or more visits throughout the study protocol (non-monotonous missing data) or when patients drop-out from the study and there is no data available of a patient after drop-out (monotonous missing data). The frequency of occurrence of these two types of missing data will be reported. If inconsistent data occurs on an individual level this will not be considered to be missing data. Out-of-range results for most behavioral outcomes are not likely to occur because computerized assessment tasks guarantee accurate data acquisition. For the behavioral observation scale the inter-rater reliability will be evaluated as a quality check. If the inter-rater reliability across all assessments made in the context of the study is lower than .70 this measure will be reported as insufficiently reliable to be used as a meaningful outcome variable. Only eye tracking data that was sufficiently accurately measured will be considered to be used as an outcome measure. Meaning that, if eye tracker calibration is not good to excellent according to the software delivered with the eye tracker after 5 repeated calibrations the eye tracking data for that assessment will be considered as missing data.
STATISTICAL ANALYSIS:
MAIN ANALYSIS: The data will be analyzed using Bayesian mixed models in R. Mixed models are the recommended approach to combine data of single cases and are increasingly acknowledged as a more powerful data analysis approach for clinical trials compared to classic ANCOVAs since mixed models can accurately model time-unstructured data. A Bayesian approach to analyze data is preferred above a classic null hypothesis significance testing because the Bayesian approach allows to quantify the strength of evidence in favor of the null hypothesis. The latter is a valuable attribute in the context of clinical trials as these studies often require proof for no difference between groups on covariates that can be assumed to affect response to treatment.
The main analysis of interest will compare the effect of the within-subject conditions placebo and active intervention. The model to estimate this effect will include the main effect of time since start of intervention condition, intervention and the counterbalancing group. In addition, the pairwise and three-way interactions of these predictors will be included. A random intercept and random slope for time will be included in the model. This model will be used to predict the primary outcome variable and the secondary outcome variables.
In addition, the association between the different outcome variables will be reported as a means to estimate to what extent treatment effects may have affected 1 specific outcome or to what extent symptom evolution across different outcome variables was associated.
66 studies on the registry are indexed under Perceptual Disorders; 21 are open to participants now.
This study's enrollment of 6 is below the median of 27 across 52 interventional studies indexed under Perceptual Disorders.
Browse Perceptual Disorders studies →KU Leuven is the lead sponsor of 373 studies on the registry; 65 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
In period 1 group A will receive the active intervention and in period 2 they will receive the placebo intervention.
Behavioral: Active Intervention · Behavioral: Placebo Intervention
In period 1 group B will receive the placebo intervention and in period 2 they will receive the active intervention.
Behavioral: Active Intervention · Behavioral: Placebo Intervention
An audiovisual expanding (looming) stimulus is presented repeatedly to patients during the intervention (Dent \& Humphreys, 2011). During the game a disk is presented to the player. This disk expands and contracts in size. The presentation of the disk coincides with the presentation of a sound that matches in frequency. The disk predicts the location where the next target will be presented. The player must discriminate between two types of target stimuli that are presented at the center of the disk. To discriminate between the two targets, the player receives a limited time window. The location of the disk and target stimuli are adjusted in real-time as a function of the player's performance. The primary goal of this algorithm is to present the multisensory looming stimuli more frequently in the contralesional field than in the ipsilesional field.
The active and placebo intervention are identical in all aspects except for the fact that stimulus presentation will be located in the center of the visual field.
Change in the Posner reaction times
A Posner paradigm is used to measure the primary outcome. Three squares with a size of 1.5°, 2 located at 7° to the left and right of the fixation cross and 1 in the center of the screen are presented. A cue is presented for 100ms. Subsequently, a target is presented 150ms or 1100ms after cue onset for 100ms, in the left or right square (size of 1.4°). Cues and targets appear on the left or right side of the screen with equal probability. The cue can be valid (i.e., same side as target) in 40% of trials, invalid (i.e., opposite to target side) in 40% of trials or not followed by a target in 20% of trials. Patients have to respond as quickly as possible when they see the target. There will be 400 experimental trials that are presented in 4 blocks of 100 trials. The order of the trials is randomized. Our primary outcome measure is the change in the response times on invalid-cued targets for the shortest SOA on the Posner task.
Time frame: The primary outcome variable is measured at 8 timepoints: First timepoint = Baseline (pre-intervention), Timepoints 2 until 6 = during intervention, Timepoint 7 = immediately after intervention, Timepoint 8 = 1 week after intervention.
Change in the Catherina Bergego Scale (CBS) score
Hemispatial neglect symptoms in daily life are measured with the Catherina Bergego scale (Azouvi et al., 2003). This scale has 10 items of behavior that are observed and given a score from 0 (= no signs of neglect) to 3 (= patient always shows signs of neglect or does not correct for it). The sum of the individual scores is the outcome index.
Time frame: This outcome variable is measured at 4 time points. Timepoint 1 = Baseline (before intervention), Timepoint 2 = during intervention, Timepoint 3 = Immediately after intervention, Timepoint 4 = 1 week after intervention.
Change in McIntosh Line Bisection endpoint weighting bias
The McIntosh line bisection task will be administered (McIntosh, 2017; McIntosh et al., 2005). There are 4 line conditions (i.e., condition A: line from -4 cm to 4cm, condition B: line from -8 to 4 cm, condition C: line from -4 to 8 and condition D: line from -8 to 8). Each line condition is presented 8 times on the page in a randomized order. The page is placed with the middle aligned to the patient's body midline. The patient is instructed to mark the middle of each line and tap the table in between each response. Performance is summarized using the endpoint weighting bias (EWB). The EWB score ranges from -1 to +1, with 0 representing the best possible score. EWB scores \< 0 indicate lower weighting of right endpoints versus left endpoints and EWB scores \> 0 indicate higher weighting of right endpoints versus left endpoints. The cut-off scores based on healthy controls are equal to -0.125 for right-sided neglect and 0.075 for left-sided neglect (McIntosh et al., 2017).
Time frame: This outcome variable is measured at 4 time points. Timepoint 1 = Baseline (before intervention), Timepoint 2 = during intervention, Timepoint 3 = Immediately after intervention, Timepoint 4 = 1 week after intervention.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Data of participants that does not contain any identifiable information and that supports the reported analysis in a publication will be made publicly available to other researchers upon request.
Supporting information: Analytic code
Time frame: The data will be made available to other researchers upon request.
Access criteria: The principal investigator will evaluate a request for sharing of individual participant data. Access criteria to the coded IPD are that the person who requests access has a profession that is associated with professional confidentiality.
Ran from May 2021 to primary completion in Aug 2023, 27 months.
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This study is terminated, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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